Synthesis, spectroscopic, DFT, anticancer evaluation and enzyme inhibition studies of platinum(II) complexes with 1-methyl-1H-1,2,3,4-tetrazole-5-thiol and phosphine ligands: Crystal structure of [Pt(mtzt)2(dppe)]

Abstract

A number of Pt(II) complexes of 1-methyl-1H-1,2,3,4-tetrazole-5-thiol (Hmtzt) with phosphine ligands have been prepared and characterized and then evaluated as potential anti-cancer and ALP enzyme inhibitor agents. The complex [Pt(mtzt)2]2 was prepared by the reaction of 1-methyl-H1-tetrazole-5-thiol (Hmtzt) with K2PtCl4. This complex was treated with equivalent molar amounts of diphosphine ligands to afford complexes of the type [Pt(mtzt)2(PPh2(CH2)nPPh2)] in good yield, {PPh2(CH2)nPPh2, where n = 1 (dppm), n = 2 (dppe), n = 3 (dppp), n = 4 (dppb) and (PPh2((C5H4)2Fe)PPh2) (dppf)}. The prepared complexes were characterized by elemental analysis, IR, 1H-{31P} and 31P-{1H} NMR spectroscopy. The resulting data suggested that the prepared complexes were mononuclear with chelating diphosphines while the mtzt ligands were monodentate coordinating via the sulfur atom to give a square planner arrangement around the Pt(II) ion. This was confirmed by a single crystal structural analysis of the [Pt(mtzt)2(dppe)] complex. The Pt(II) complexes underwent structural optimization through the utilization of the DMol3 tool within the material studio package. A comparison of the results of molecular modelling with those of the X-ray structural analysis indicated that the structures were almost identical. The free ligand and two selected complexes were tested for inhibition activity against an alkaline phosphatase (ALP) enzyme, which was found to be active inhibitors, and the inhibition rate (37–88 %) range. Furthermore, the anticancer activity of the complexes (1, 3, and 6) was tested against human liver cancer (HepG2). The results showed that the prepared complexes have moderate activity but are lower than cis-platin. Complex 1 has the highest activity with an IC50 of 34.78 ± 1.75 M against the HepG2 cell line..